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1.  Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women 
Mediators of Inflammation  2015;2015:516783.
Background. Since high sensitivity C-reactive protein (hsCRP) is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD) etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG) and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF) may have a role in CVD. Methods and Results. We examined BDNF levels in 3 groups of women that were age- and race-matched with low (<3 mg/L), mid (>3–20 mg/L), and high (>20 mg/L) hsCRP (n = 39 per group) and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. Conclusion. We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3 mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP.
PMCID: PMC4460236  PMID: 26161003
2.  Opportunities for Cancer Prevention Among Adults Aged 45 to 64 
American journal of preventive medicine  2014;46(3 0 1):S87-S97.
Despite the advances in cancer medicine and the resultant 20% decline in cancer death rates for Americans since 1991, there remain distinct cancer health disparities among African Americans, Hispanics, Native Americans, and the those living in poverty. Minorities and the poor continue to bear the disproportionate burden of cancer especially in terms of stage at diagnosis, incidence and mortality. Cancer health disparities are persistent reminders that state-of-the art cancer prevention, diagnosis, and treatment are not equally effective for and accessible to all Americans.
The cancer prevention model must take into account the phenotype of accelerated aging associated with health disparities as well as the important interplay of biological and sociocultural factors that lead to disparate health outcomes. The building blocks of this prevention model will include: interdisciplinary prevention modalities that encourage partnerships across medical and nonmedical entities, community-based participatory research, development of ethnically and racially diverse research cohorts, and full actualization of the prevention benefits outlined in the 2010 Patient Protection and Affordable Care Act. However, the most essential facet should be a thoughtful integration of cancer prevention and screening into prevention, screening, and disease management activities for hypertension and diabetes mellitus since these chronic medical illnesses have a substantial prevalence in populations at risk for cancer disparities and cause considerable comorbidity and likely complicate effective treatment and contribute to disproportionate cancer death rates.
PMCID: PMC4431696  PMID: 24512936
3.  Alzheimer’s Disease Associated Polymorphisms in Human OGG1 Alter Catalytic Activity and Sensitize Cells to DNA Damage 
Brain tissues from Alzheimer’s Disease (AD) patients show increased levels of oxidative DNA damage and 7,8-dihydro-8-oxoguanine (8-oxoG) accumulation. In humans, the base excision repair protein 8-oxoguanine-DNA glycosylase (OGG1) is the major enzyme that recognizes and excises the mutagenic DNA base lesion 8-oxoG. Recently, two polymorphisms of OGG1, A53T and A288V, have been identified in brain tissues of AD patients, but little is known about how these polymorphisms may contribute to AD. We characterized the A53T and A288V polymorphic variants and detected a significant reduction in the catalytic activity for both proteins in vitro and in cells. Additionally, the A53T polymorphism has decreased substrate binding, while the A288V polymorphism has reduced AP lyase activity. Both variants have decreased binding to known OGG1 binding partners PARP-1 and XRCC1. We found that OGG1−/− cells expressing A53T and A288V OGG1 were significantly more sensitive to DNA damage and had significantly decreased survival. Our results provide both biochemical and cellular evidence that A53T and A288V polymorphic proteins have deficiencies in catalytic and protein binding activities that could be related to the increase in oxidative damage to DNA found in AD brains.
PMCID: PMC3767440  PMID: 23684897
8-oxoguanine-DNA glycosylase (OGG1); DNA damage; DNA repair; oxidative stress; 8-oxoguanine (8-oxoG); base excision repair (BER); Alzheimer’s Disease
4.  Personality Assessment in a Diverse Urban Sample 
Psychological assessment  2013;25(3):1007-1012.
The present research examined the data quality and replicability of the Revised NEO Personality Inventory (NEO-PI-R) factor structure in a sample that varied in ethnicity, socioeconomic status, and literacy. Participants (N=546), drawn from the Healthy Aging in Neighborhoods of Diversity across the Life Span study, were African American (58%) and White (42%) urban dwellers living above (49%) and below (51%) 125% of the federal poverty line. The NEO-PI-R, administered via telephone, was evaluated for data quality (percent valid, acquiescence, internal consistency), congruence with the normative factor structure, and readability. All indices of data quality and factor congruence were excellent in the full sample. Literacy was the most consistent predictor of data quality. A slightly worse structure was found for the Openness to Experience and Extraversion factors among lower SES African American and White participants. The overall index of factor congruence, however, supports replication of the normative structure well beyond chance levels even among those with lower literacy. Despite the challenges of low literacy, the present findings indicate that personality traits can be assessed reliably in socioeconomically diverse populations that include those living in poverty.
PMCID: PMC3790259  PMID: 23815114
Personality assessment; psychometrics; literacy; Openness to Experience; Socioeconomic status
5.  Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease 
Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant.
PMCID: PMC3664937  PMID: 23428415
DNA oxidation; RNA oxidation; Protein oxidation; Single Strand Breaks; CRP
6.  Age-related changes in microRNA levels in serum 
Aging (Albany NY)  2013;5(10):725-740.
microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFα and to correlate positively with the anti-inflammatory cytokines TGFβ and IL-10. These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age.
PMCID: PMC3838776  PMID: 24088671
circulating; miRNA; noncoding RNA; age; aging; biomarker; exRNA; extracellular RNA
7.  Coordination of DNA repair by NEIL1 and PARP-1: a possible link to aging 
Aging (Albany NY)  2012;4(10):674-685.
Oxidative DNA damage accumulates with age and is repaired primarily via the base excision repair (BER) pathway. This process is initiated by DNA glycosylases, which remove damaged bases in a substrate-specific manner. The DNA glycosylases human 8-oxoguanine-DNA glycosylase (OGG1) and NEIL1, a mammalian homolog of Escherichia coli endonuclease VIII, have overlapping yet distinct substrate specificity. Recently, we reported that OGG1 binds to the Poly(ADP-ribose) polymerase 1 (PARP-1), a DNA damage sensor protein that poly(ADP-ribosyl)ates nuclear proteins in response to DNA damage and other cellular signals. Here, we show that NEIL1 and PARP-1 bind both in vitro and in vivo. PARP-1 binds to the C-terminal-100 amino acids of NEIL1 and NEIL1 binds to the BRCT domain of PARP-1. NEIL1 stimulates the poly(ADP-ribosyl)ation activity of PARP-1. Furthermore, NEIL-deficient fibroblasts have impaired poly(ADP-ribosyl)ation of cellular proteins after DNA damage, which can be rescued by NEIL1 expression. Additionally, PARP-1 inhibits NEIL1 incision activity in a concentration-dependent manner. Consistent with the idea of impaired DNA repair during aging, we observed differential binding of PARP-1 to recombinant NEIL1 in older mice compared to younger mice. These data further support the idea that dynamic interplay between different base excision repair proteins is important for efficient BER.
PMCID: PMC3517938  PMID: 23104860
PARP; base excision repair; DNA damage; oxidative stress; aging; glycosylase
8.  Neighborhood Racial Composition, Racial Discrimination, and Depressive Symptoms in African Americans 
While evidence indicates that experienced racial discrimination is associated with increased depressive symptoms for African Americans, there is little research investigating predictors of experienced racial discrimination. This paper examines neighborhood racial composition and sociodemographic factors as antecedents to experienced racial discrimination and resultant levels of depressive symptoms among African American adults. The sample included 505 socioeconomically-diverse African American adults from Baltimore, MD. Study data were obtained via self-report and geocoding of participant addresses based on 2010 census data. Study hypotheses were tested using multiple pathways within a longitudinal Structural Equation Model. Experienced racial discrimination was positively associated with age and sex such that older individuals and males experienced increased levels of racial discrimination. In addition, the percentage of White individuals residing in a neighborhood was positively associated with levels of experienced racial discrimination for African American neighborhood residents. Experienced racial discrimination was positively associated with later depressive symptoms. Neighborhood-level contextual factors such as neighborhood racial composition and individual differences in sociodemographic characteristics appear to play an important role in the experience of racial discrimination and the etiology of depression in African American adults.
PMCID: PMC4501853  PMID: 24969707
Racial discrimination; African American; Neighborhood racial composition; Sociodemographics; Racial health disparities
9.  Meta-analysis of loci associated with age at natural menopause in African-American women 
Human Molecular Genetics  2014;23(12):3327-3342.
Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.
PMCID: PMC4030781  PMID: 24493794
10.  Perceived Sex Discrimination Amplifies the Effect of Antagonism on Cigarette Smoking 
Nicotine & Tobacco Research  2014;16(6):794-799.
Compared to men, the decline in smoking during the past few decades has been slower for women, and smoking-related morbidity and mortality has increased substantially. Identifying sex-specific risk factors will inform more targeted intervention/prevention efforts. The purpose of this research is to examine the interactive effect of psychological (trait antagonism) and social (perceived sex discrimination) factors on current cigarette smoking and whether these effects differ by sex.
Participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS; N = 454) and participants in the Health and Retirement Study (HRS; N = 8,155) completed measures of antagonism, perceived sex discrimination, and reported whether they smoked currently. Logistic regressions were used to predict smoking from antagonism, discrimination, and their interaction.
Antagonism was associated with an increased risk of smoking. For women, there was an interaction between antagonism and discrimination: among women who perceived sex discrimination, every standard deviation increase in antagonism was associated with a 2.5 increased risk of current smoking in HANDLS (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.46–4.39) and an almost 1.5 increased risk in HRS (OR = 1.43, 95% CI = 1.18–1.73). This interaction was not significant for men in either sample.
In 2 independent samples, perceived sex discrimination amplified the effect of antagonism on cigarette smoking for women but not men. A hostile disposition and a perceived hostile social environment have a synergistic effect on current cigarette smoking for women.
PMCID: PMC4015093  PMID: 24477195
11.  Genetic loci for serum magnesium among African-Americans and gene-environment interaction at MUC1 and TRPM6 in European-Americans: the Atherosclerosis Risk in Communities (ARIC) study 
BMC Genetics  2015;16:56.
Low serum magnesium levels have been associated with multiple chronic diseases. The regulation of serum magnesium homeostasis is not well understood. A previous genome-wide association study (GWAS) of European ancestry (EA) populations identified nine loci for serum magnesium. No such study has been conducted in African-Americans, nor has there been an evaluation of the interaction of magnesium-associated SNPs with environmental factors. The goals of this study were to identify genetic loci associated with serum magnesium in an African-American (AA) population using both genome-wide and candidate region interrogation approaches and to evaluate gene-environment interaction for the magnesium-associated variants in both EA and AA populations. We conducted a GWAS of serum magnesium in 2737 AA participants of the Atherosclerosis Risk in Communities (ARIC) Study and interrogated the regions of the nine published candidate loci in these results. Literature search identified the influence of progesterone on MUC1 expression and insulin on TRPM6 expression.
The GWAS approach in African-American participants identified a locus near MUC1 as genome-wide significant (rs2974937, beta = −0.013, p = 6.1x10−9). The candidate region interrogation approach identified two of the nine loci previously discovered in EA populations as containing SNPs that were significantly associated in African-American participants (SHROOM3 and TRPM6). The index variants at these three loci together explained 2.8 % of the variance in serum magnesium concentration in ARIC African-American participants. On the test of gene-environment interaction in ARIC EA participants, the index variant at MUC1 had 2.5 times stronger association in postmenopausal women with progestin use (beta = −0.028, p = 7.3x10−5) than in those without any hormone use (beta = −0.011, p = 7.0x10−8, p for interaction 0.03). At TRPM6, the index variant had 1.6 times stronger association in those with lower fasting insulin levels (<80pmol/L: beta = −0.013, p = 1.6x10−7; ≥80pmol/L: beta = −0.008, p = 1.8x10−2, p for interaction 0.03).
We identified three loci that explained 2.8 % of the variance in serum magnesium concentration in ARIC African-American participants. Following-up on functional studies of gene expression identified gene-environment interactions between progestin use and MUC1 and between insulin and TRPM6 on serum magnesium concentration in ARIC European-American participants. These results extend our understanding of the metabolism of serum magnesium.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0219-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4462077  PMID: 26058915
Gene-environment interaction; Serum magnesium; MUC1; TRPM6
12.  Recruitment and Retention Strategies for Minority or Poor Clinical Research Participants: Lessons From the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study 
The Gerontologist  2011;51(Suppl 1):S33-S45.
Purpose of the study: Investigating health disparities requires studies designed to recruit and retain racially and socioeconomically diverse cohorts. It is critical to address the barriers that disproportionately affect participation in clinical research by minorities and the socioeconomically disadvantaged. This study sought to identify and rectify these barriers to recruit and retain a biracial (African American and non-Hispanic White) and socioeconomically diverse cohort for a longitudinal study. Design and Method: The Healthy Aging in Neighborhoods of Diversity across the Life Span study is a 20-year longitudinal examination of how race and socioeconomic status influence the development of age-related health disparities. One goal was to create a multifactorial recruitment and retention strategy. The recruitment paradigm targeted known barriers and identified those unique to the study's urban environment. The retention paradigm mirrored the recruitment plan but was based on specifically developed approaches. Results: This cohort recruitment required attention to developing community partnerships, designing the research study to meet the study hypotheses and to provide benefit to participants, providing a safe community-based site for the research and creating didactics to develop staff cultural proficiency. These efforts facilitated study implementation and enhanced recruitment resulting in accrual of a biracial and socioeconomically diverse cohort of 3,722 participants. Implications: Recruiting and retaining minority or poor research participants is challenging but possible. The essential facets include clear communication of the research hypothesis, focus on providing a direct benefit for participants, and selection of a hypothesis that is directly relevant to the community studied
PMCID: PMC3092978  PMID: 21565817
Cultural proficiency; Health disparities; Community-based research platform
13.  Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS): Overcoming barriers to implementing a longitudinal, epidemiologic, urban study of health, race, and socioeconomic status 
Ethnicity & disease  2010;20(3):267-275.
Examine the influences of race, socioeconomic status, sex, and age on barriers to participation in a study of cross-sectional differences and longitudinal changes in health-related outcomes.
We designed a multidisciplinary, community-based, prospective longitudinal epidemiologic study among socioeconomically diverse African Americans and whites. The study protocol facilitated our ability to recruit 3722 participants from Baltimore, MD with mean age 47.7 (range 30–64) years, % males/female, 2200 African Americans (59%) and 1522 whites (41%); 41% reported household incomes below the 125% poverty delimiter.
There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. Age, race, and sex, but not poverty status, were associated with the likelihood of an examination. Older participants, women, and whites were more likely to complete their examinations. Among those who completed their examinations, there were no age differences associated with sex and poverty status, but African Americans were negligibly younger than whites.
Although some literature suggests that minorities and low-income people are less willing to participate in clinical research, these baseline data suggest that African Americans individuals and individuals from households with incomes below 125% of the poverty level are at least as willing to participate in observational clinical studies as whites and higher income individuals of similar age and sex.
PMCID: PMC3040595  PMID: 20828101
Healthcare disparities; socioeconomic status; Population groups; Epidemiologic research design; Health surveys; Longitudinal studies
14.  A novel R229Q OGG1 polymorphism results in a thermolabile enzyme that sensitizes KG-1 leukemia cells to DNA damaging agents 
Cancer detection and prevention  2007;31(3):237-243.
Mutations and polymorphisms of OGG1, the major mammalian 8-oxoguanine repair activity, are associated with increased risk for several cancers. Decreased 8-oxoguanine repair capacity due to variant forms of the OGG1 gene is a common feature of numerous cancer cell lines. One such cell line, human KG-1 leukemia cells, has previously been demonstrated to be deficient in the excision of 8-oxoguanine from oxidatively damaged DNA. KG-1 cells have a homozygous R229Q amino acid substitution in OGG1 that has been presumed to alter the function of OGG1 and result in elevated levels of genomic 8-oxoG and hypersensitivity to 8-hydroxydeoxyguanosine nucleoside and ionizing radiation observed in KG-1 cells.
We characterized the enzymatic activity of R229Q OGG1 and the effect of the enzyme on cell survival following treatment with DNA damaging agents.
R229Q OGG1 had activity similar to the wild-type enzyme, yet was easily heat inactivated at physiological temperature. R229Q OGG1 expressed in human cells had significantly lower activity than wild-type OGG1 and was also highly thermolabile. Expression of R229Q OGG1 sensitized KG-1 cells to killing by menadione and 8-hydroxydeoxyguanosine, but not ionizing radiation.
These results suggest that decreased 8-oxoguanine repair in KG-1 is due to thermolability of R229Q OGG1 and that the enzyme variant increases cellular susceptibility to killing resulting from oxidative DNA damage. The R229Q OGG1 variant is a validated polymorphism prevalent in world populations and not an isolated mutation in KG-1 cells, thus the R229Q OGG1 allele may be a novel marker for cancer susceptibility.
PMCID: PMC2699023  PMID: 17651912
R229Q; OGG1; 8-oxoguanine; KG-1; leukemia; polymorphism
15.  OGG1 is degraded by calpain following oxidative stress and cisplatin exposure 
DNA repair  2008;7(4):648-654.
Deficient repair activity for 8-hydroxy-2′-deoxyguanine (8-oxoguanine), a premutagenic oxidative DNA damage, has been observed in affected tissues in neurodegenerative diseases of aging, such as Alzheimer’s disease, and in ischemia/reperfusion injury, type 2 diabetes mellitus, and cancer. These conditions have in common the accumulation of oxidative DNA damage, which is believed to play a role in disease progression, and loss of intracellular calcium regulation. These observations suggest that oxidative DNA damage repair capacity may be influenced by fluctuations in cellular calcium. We have identified human 8-oxoguanine-DNA glycosylase 1 (OGG1), the major 8-oxoguanine repair activity, as a specific target of the Ca2+-dependent protease Calpain I. Protein sequencing of a truncated partially calpain-digested OGG1 revealed that calpain recognizes OGG1 for degradation at a putative PEST (Proline, Glutamic acid, Serine, Threonine) sequence in the C-terminus of the enzyme. Co-immunoprecipitation experiments showed that OGG1 and Calpain I are associated in human cells. Exposure of HeLa cells to hydrogen peroxide or cisplatin resulted in the degradation of OGG1. Pretreatment of cells with the calpain inhibitor calpeptin resulted in inhibition of OGG1 proteolysis and suggests that OGG1 is a target for calpain-mediated degradation in vivo during oxidative stress- and cisplatin-induced apoptosis. Polymorphic OGG1 S326C was comparatively resistant to calpain digestion in vitro, yet was also degraded by a calpain-dependent pathway in vivo following DNA damaging agent exposure. The degradation of OGG1 by calpain may contribute to decreased 8-oxoguanine repair activity and elevated levels of 8-oxoguanine reported in tissues undergoing chronic oxidative stress, ischemia/reperfusion and other cellular stressors known to produce perturbations of intracellular calcium homeostasis which activate calpain.
PMCID: PMC2699025  PMID: 18294929
OGG1; calpain; 8-oxoguanine; calcium; PEST
16.  Apolipoprotein L1, income and early kidney damage 
BMC Nephrology  2015;16:14.
The degree to which genetic or environmental factors are associated with early kidney damage among African Americans (AAs) is unknown.
Among 462 AAs in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, we examined the cross-sectional association between apolipoprotein L1 (APOL1) risk variants and income with: 1) mildly reduced eGFR (<75 mL/min/1.73 m2, creatinine-cystatin C equation) and 2) elevated urine albumin-to-creatinine ratio (ACR) (≥17 in men and ≥25 mg/g in women). High risk APOL1 status was defined by 2 copies of high-risk variants; low risk if 0 or 1 copy. Income groups were dichotomized as < $14,000/year (lowest income group) or ≥ $14,000/year. Logistic regression models were adjusted for age, sex, and % European ancestry.
Overall, participants’ mean age was 47 years and 16% (n = 73) had high risk APOL1 status. Mean eGFR was 99 mL/min/1.73 m2. Mildly reduced eGFR was prevalent among 11% (n = 51). The lowest income group had higher adjusted odds (aOR) of mildly reduced eGFR than the higher income group (aOR 1.8, 95% CI 1.2-2.7). High-risk APOL1 was not significantly associated with reduced eGFR (aOR 1.5, 95% CI 0.9-2.5). Among 301 participants with ACR data, 7% (n = 21) had elevated ACR. Compared to low-risk, persons with high-risk APOL1 had higher odds of elevated ACR (aOR 3.8, 95% CI 2.0-7.3). Income was not significantly associated with elevated ACR (aOR 1.8, 95% CI 0.7-4.5). There were no significant interactions between APOL1 and income.
Both genetic and socioeconomic factors may be important determinants of early kidney damage among AAs.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0008-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4361142  PMID: 25884165
APOL1; Chronic kidney disease; Socioeconomic status; African American; Renal; Albuminuria
17.  Effect of Food Insecurity on Chronic Kidney Disease in Lower Income Americans 
American journal of nephrology  2014;39(1):27-35.
The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower income individuals in both the general U.S. adult population and an urban population.
We conducted cross-sectional analyses of lower income participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2008 (n=9,126); and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n=1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression.
In NHANES, the age-adjusted prevalence of CKD was 20.3%, 17.6% and 15.7% for the high, marginal and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.14–2.45 comparing high to no food insecurity group] or hypertension (OR 1.37, 95% CI 1.03–1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9% and 4.6% for those with and without food insecurity, respectively (P=0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR 1.46, 95% CI 0.98–2.18) with no evidence of effect modification across diabetes, hypertension or obesity subgroups.
Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.
PMCID: PMC3952065  PMID: 24434743
renal; socioeconomic status; disparity; nutrition
18.  Diet quality inversely associated with C-reactive protein levels in urban, low-income African American and White adults 
Journal of the Academy of Nutrition and Dietetics  2013;113(12):10.1016/j.jand.2013.07.004.
C-Reactive Protein (CRP), an inflammatory biomarker, is influenced by many factors including socioeconomic position, genetics and diet. The inverse association between diet and CRP is biologically feasible because micronutrients with antioxidative properties may enable the body to manage the balance between production and accumulation of reactive species that cause oxidative stress.
To determine the quality of the diet consumed by urban, low-income African American and White adults aged 30 to 64 years, and association of diet quality with CRP.
Data from a cross-sectional study were used to evaluate diet quality assessed by mean adequacy ratio (MAR). Two 24-hour recalls were collected by trained interviewers using the USDA automated multiple pass method.
The sample consisted of Healthy Aging in Neighborhoods of Diversity across the Life Span baseline study participants, 2004–2009, who completed both recalls (n=2017).
Main outcome measures
MAR equaled the average of the ratio of intakes to RDA for 15 vitamins and minerals. CRP levels were assessed by the nephelometric method utilizing latex particles coated with CRP monoclonal antibodies.
Statistical analysis performed
Linear ordinary least square regression and generalized linear models were performed to determine the association of MAR (independent variable) with CRP (dependent variable) while adjusting for potential confounders.
MAR scores ranged from 74.3 to 82.2. Intakes of magnesium and Vitamins A, C, and E were the most inadequate compared to Estimated Average Requirements. CRP levels were significantly associated with MAR, DXA-measured body fat, and hypertension. A 10% increase in MAR was associated to a 4% decrease in CRP.
The MAR was independently and significantly inversely associated with CRP, suggesting diet is associated with the regulation of inflammation. Interventions to assist people make better food choices may not only improve diet quality but also their health, possibly reducing risk for cardiovascular disease.
PMCID: PMC3833870  PMID: 24035460
19.  Sodium Intake of Special Populations in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Study 
Preventive medicine  2013;57(4):334-338.
The sodium intake of participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were in three of the special population groups identified by the Dietary Guidelines for Americans, 2010 (those with hypertension, African Americans, and those ≥51 years) was analyzed to determine if they met sodium recommendations.
The sample included 2152 African American and White subjects, aged 30-64 years. Major dietary sources of sodium for each group were determined from two 24-hour dietary recalls, and dietary intakes were compared with sodium recommendations. Dietary potassium was also evaluated.
The intakes of the groups studied exceeded 1500 mg sodium while their potassium intakes were lower than the Adequate Intake of 4700 mg. The major contributors of sodium included “cold cuts, sausage, and franks,” “protein foods”, and yeast breads.
Excessive sodium intake characterized the diet of an urban, socioeconomically diverse population who are hypertensive or at risk for having hypertension. These findings have implications for health professionals and the food industry.
PMCID: PMC3775971  PMID: 23769900
nutrition/diet; hypertension; health promotion; public health; prevention; lifestyle modification/health behavior
20.  Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes 
Ng, Maggie C. Y. | Shriner, Daniel | Chen, Brian H. | Li, Jiang | Chen, Wei-Min | Guo, Xiuqing | Liu, Jiankang | Bielinski, Suzette J. | Yanek, Lisa R. | Nalls, Michael A. | Comeau, Mary E. | Rasmussen-Torvik, Laura J. | Jensen, Richard A. | Evans, Daniel S. | Sun, Yan V. | An, Ping | Patel, Sanjay R. | Lu, Yingchang | Long, Jirong | Armstrong, Loren L. | Wagenknecht, Lynne | Yang, Lingyao | Snively, Beverly M. | Palmer, Nicholette D. | Mudgal, Poorva | Langefeld, Carl D. | Keene, Keith L. | Freedman, Barry I. | Mychaleckyj, Josyf C. | Nayak, Uma | Raffel, Leslie J. | Goodarzi, Mark O. | Chen, Y-D Ida | Taylor, Herman A. | Correa, Adolfo | Sims, Mario | Couper, David | Pankow, James S. | Boerwinkle, Eric | Adeyemo, Adebowale | Doumatey, Ayo | Chen, Guanjie | Mathias, Rasika A. | Vaidya, Dhananjay | Singleton, Andrew B. | Zonderman, Alan B. | Igo, Robert P. | Sedor, John R. | Kabagambe, Edmond K. | Siscovick, David S. | McKnight, Barbara | Rice, Kenneth | Liu, Yongmei | Hsueh, Wen-Chi | Zhao, Wei | Bielak, Lawrence F. | Kraja, Aldi | Province, Michael A. | Bottinger, Erwin P. | Gottesman, Omri | Cai, Qiuyin | Zheng, Wei | Blot, William J. | Lowe, William L. | Pacheco, Jennifer A. | Crawford, Dana C. | Grundberg, Elin | Rich, Stephen S. | Hayes, M. Geoffrey | Shu, Xiao-Ou | Loos, Ruth J. F. | Borecki, Ingrid B. | Peyser, Patricia A. | Cummings, Steven R. | Psaty, Bruce M. | Fornage, Myriam | Iyengar, Sudha K. | Evans, Michele K. | Becker, Diane M. | Kao, W. H. Linda | Wilson, James G. | Rotter, Jerome I. | Sale, Michèle M. | Liu, Simin | Rotimi, Charles N. | Bowden, Donald W.
PLoS Genetics  2014;10(8):e1004517.
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94
Author Summary
Despite the higher prevalence of type 2 diabetes (T2D) in African Americans than in Europeans, recent genome-wide association studies (GWAS) were examined primarily in individuals of European ancestry. In this study, we performed meta-analysis of 17 GWAS in 8,284 cases and 15,543 controls to explore the genetic architecture of T2D in African Americans. Following replication in additional 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry, we identified two novel and three previous reported T2D loci reaching genome-wide significance. We also examined 158 loci previously reported to be associated with T2D or regulating glucose homeostasis. While 56% of these loci were shared between African Americans and the other populations, the strongest associations in African Americans are often found in nearby single nucleotide polymorphisms (SNPs) instead of the original SNPs reported in other populations due to differential genetic architecture across populations. Our results highlight the importance of performing genetic studies in non-European populations to fine map the causal genetic variants.
PMCID: PMC4125087  PMID: 25102180
Drug and alcohol dependence  2012;131(3):247-251.
Illicit substances increase risk of morbidity and mortality and have significant consequences for society. Personality traits are associated with drug use; we test whether these associations vary by socioeconomic status.
Participants (N=412) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study completed the Revised NEO Personality Inventory and self-reported use of opiates and cocaine. 50% of participants were living below 125% of the federal poverty line. Mean-level personality differences across never, former, and current opiate/cocaine users were compared. Logistic regressions compared never versus current users and interactions between personality traits and poverty status tested whether these associations varied by socioeconomic status.
High Neuroticism and low Agreeableness increased risk of drug use. The association between low Conscientiousness and drug use was moderated by poverty, such that low Conscientiousness was a stronger risk factor for illicit substance use among those with relatively higher SES: For every standard deviation decrease in Conscientiousness, there was a greater than 2-fold increase in risk of illicit substance use (OR=2.15, 95% CI=1.45–3.17). Conscientiousness was unrelated to drug use among participants living below 125% of the federal poverty line.
Under favorable economic conditions, the tendency to be organized, disciplined, and deliberate is protective against drug use. These tendencies, however, matter less when financial resources are scarce. In contrast, those prone to emotional distress and antagonism are at greater risk for current drug use, regardless of their economic situation.
PMCID: PMC3610771  PMID: 23265091
personality traits; conscientiousness; substance use; poverty; cocaine; heroin
Mutation research  2012;736(0):93-103.
It is well accepted that oxidative DNA repair capacity, oxidative damage to DNA and oxidative stress play central roles in aging and disease development. However, the correlation between oxidative damage to DNA, markers of oxidant stress and DNA repair capacity is unclear. In addition, there is no universally accepted panel of markers to assess oxidative stress in humans. Our interest is oxidative damage to DNA and its correlation with DNA repair capacity and other markers of oxidative stress. We present preliminary data from a small comet study that attempts to correlate single strand break (SSB) level with single strand break repair capacity (SSB-RC) and markers of oxidant stress and inflammation. In this limited study of four very small age-matched 24-individual groups of male and female whites and African-Americans aged 30–64 years, we found that females have higher single strand break (SSB) levels than males (p=0.013). There was a significant negative correlation between SSB-RC and SSB level (p=0.041). There was a positive correlation between SSBs in African American males with both heme degradation products (p=0.008) and high-sensitivity C-reactive protein (hs-CRP) (p=0.022). We found a significant interaction between hs-CRP and sex in their effect on residual DNA damage (p=0.002). Red blood cell reduced glutathione concentration was positively correlated with the levels of oxidized bases detected by endonuclease III (p=0.047), heme degradation products (p=0.015) and hs-CRP (p=0.020). However, plasma carbonyl levels showed no significant correlation with other markers. The data from the literature and from our very limited study suggest a complex relationship between measures of oxidative stress and frequently used clinical parameters believed to reflect inflammation or oxidative stress.
PMCID: PMC4037702  PMID: 22273780
oxidative stress; aging; DNA oxidative lesions; DNA repair; comet assay; red blood cell glutathione (RBC GSH); fluorescent heme degradation products; high-sensitivity C-reactive protein (hs-CRP)
The New England journal of medicine  2013;369(21):1991-2000.
Low levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D–binding protein has not been considered in the assessment of vitamin D deficiency.
In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D–binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D–binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants.
Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D–binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D–binding protein, 168±3 μg per milliliter vs. 337±5 μg per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D–binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxy vitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P = 0.71) and within quintiles of parathyroid hormone concentration.
Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D–binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.)
PMCID: PMC4030388  PMID: 24256378
Circulation. Cardiovascular genetics  2012;5(4):10.1161/CIRCGENETICS.111.961813.
African Americans suffer from higher prevalence and severity of atherosclerosis compared to Whites, highlighting racial and ethnic disparities in cardiovascular disease. Previous studies have pointed to the role of vascular inflammation and platelet activation in the formation of atherosclerotic lesions.
Methods and Results
We explored the role of genetic variation in four chemokine/chemokine receptor genes (CX3CR1, CX3CL1, CXCR3 and PF4) on systemic inflammation and platelet activation serum biomarkers (fractalkine, platelet P-selectin, PF4 and TNFα). In total, 110 SNPs were tested among 1,042 African Americans and 763 Whites. The strongest association with serum PF4 levels was observed for rs168449, which was significant in both racial groups (P-value: African Americans=0.0017, Whites=0.014, Combined=1.2×10−4), and remained significant after permutation-based multiple corrections (Pc-value: Combined=0.0013). After accounting for the effect of rs168449, we identified another significant SNP (rs1435520) suggesting a second independent signal regulating serum PF4 levels (conditional P-value: African Americans=0.02, Whites=0.02). Together these SNPs explained 0.98% and 1.23% of serum PF4 variance in African Americans and Whites, respectively. Additionally, in African Americans, we found an additional PF4 variant (rs8180167), uncorrelated with rs168449 and rs1435520, associated with serum TNFα levels (P-value=0.008, Pc-value=0.048).
Our study highlight the importance of PF4 variants in the regulation of platelet activation (PF4) and systemic inflammation (TNFα) serum biomarkers.
PMCID: PMC3864008  PMID: 22763266
association study; atherosclerosis; inflammation; platelets; Chemokines; PF4; TNF-alpha
Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval.
Methods and Results
First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5×10−8) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2×10−15) and ATP1B1 (rs1320976, p=2×10−10). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10−5) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN.
We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
PMCID: PMC3568265  PMID: 23166209
electrocardiography; electrophysiology; genome-wide association studies; ion channels; repolarization

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